rs150425166
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_024334.3(TMEM43):c.484G>A(p.Asp162Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,758 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D162G) has been classified as Uncertain significance.
Frequency
Consequence
NM_024334.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM43 | NM_024334.3 | c.484G>A | p.Asp162Asn | missense_variant | 6/12 | ENST00000306077.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM43 | ENST00000306077.5 | c.484G>A | p.Asp162Asn | missense_variant | 6/12 | 1 | NM_024334.3 | P1 | |
TMEM43 | ENST00000432444.2 | c.*514G>A | 3_prime_UTR_variant, NMD_transcript_variant | 7/13 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 152158Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251460Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135914
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461600Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 727120
GnomAD4 genome ? AF: 0.000191 AC: 29AN: 152158Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74328
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 14, 2014 | Variant classified as Uncertain Significance - Favor Benign. The Asp162Asn varia nt in TMEM43 has not been previously reported in individuals with cardiomyopathy , but has been identified in 0.2% (7/4406) of African American chromosomes by th e NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs150 425166). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, while the c linical significance of the Asp162Asn variant is uncertain, its frequency sugges ts that it is more likely to be benign. - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 20, 2023 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 08, 2022 | - - |
Arrhythmogenic right ventricular dysplasia 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2022 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at